# A retrospective analysis exploring the association of pretreatment neutrophil-to-lymphocyte ratio and immune checkpoint inhibitor outcomes in patients with advanced NSCLC and liver metastases

## TL;DR

Patients with lung cancer and liver metastases who have high blood inflammation levels respond worse to immunotherapy.

## Contribution

This study identifies NLR as a potential biomarker for predicting immunotherapy outcomes in NSCLC patients with liver metastases.

## Key findings

- Patients with liver metastases had significantly higher NLR and worse survival outcomes on immunotherapy.
- NSCLC patients with both liver metastases and high NLR had the shortest progression-free and overall survival.
- The negative impact of high NLR was observed even in patients with high PD-L1 expression.

## Abstract

Liver metastases (LM) in advanced non-small-cell lung cancer (NSCLC) are associated with poor clinical outcomes. The tolerogenic immune microenvironment in the liver may contribute to inferior response to immune checkpoint inhibitors (ICIs). We hypothesized that the presence of LM may be associated with an expanded peripheral myeloid population, using the neutrophil-to-lymphocyte ratio (NLR) as a surrogate in patients treated with ICIs.

We evaluated the impact of LM and NLR on clinical outcomes in patients with advanced NSCLC treated with ICIs.

This was a retrospective analysis conducted at a single cancer center.

We reviewed the records of 324 patients with advanced NSCLC treated with programmed death ligand-1 (PD-L1) inhibitors as monotherapy or in combination with cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were evaluated among patients with and without LM in NLR-High (NLR ⩾ 5) and NLR-Low (NLR < 5) subgroups.

Patients with LM had significantly higher median NLR compared to patients without LM (median 7.3 vs 4.5, p < 0.001). Patients with LM had significantly shorter median PFS (HR 1.54, p = 0.006) and median OS (HR 1.56, p = 0.014). Patients with LM who were NLR-High (LM+ NLR-H) had shorter median PFS and median OS (2.0 months and 5.4 months, respectively) compared to patients who had LM and were NLR-Low (LM+ NLR-L, median PFS 4.0 months and median OS 13.3 months). This trend was also observed within the PD-L1 > 50% subgroup. In 42 patients with evaluable response and LM, 25/42 (59.5%) of patients had concordant responses in the liver and extra-hepatic sites.

Patients with LM who are NLR-High had the poorest clinical outcomes to ICI, and this appeared to be irrespective of PD-L1 status. Ongoing translational work will provide further insight into tumor myeloid subpopulations that may correlate with treatment resistance.

Liver metastases and blood inflammatory marker NLR predict patient outcomes with immunotherapy in lung cancer treatment

In patients with advanced non-small cell lung cancer (NSCLC), those with disease spread to the liver tend to respond poorly to immunotherapy. This study looked at the whether blood test values of neutrophil-to-lymphocyte ratios (NLR), reflecting inflammatory status, can help explain this. We reviewed data from 324 patients treated with immunotherapy and found that patients with liver metastases had higher NLRs and worse outcomes. In particular, patients with both liver metastases and high NLR had the shortest survival. These findings suggest that inflammation status, as reflected by NLR, may play a role in predicting poor response to immunotherapy in this group. Future studies will focus on further understanding at the molecular level.

Graphical Abstract